rs372115693
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006371.5(CRTAP):c.92A>G(p.Tyr31Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,590,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y31Y) has been classified as Likely benign.
Frequency
Consequence
NM_006371.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRTAP | NM_006371.5 | c.92A>G | p.Tyr31Cys | missense_variant | 1/7 | ENST00000320954.11 | |
CRTAP | NM_001393363.1 | c.92A>G | p.Tyr31Cys | missense_variant | 1/6 | ||
CRTAP | NM_001393364.1 | c.92A>G | p.Tyr31Cys | missense_variant | 1/6 | ||
CRTAP | NM_001393365.1 | c.92A>G | p.Tyr31Cys | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRTAP | ENST00000320954.11 | c.92A>G | p.Tyr31Cys | missense_variant | 1/7 | 1 | NM_006371.5 | P1 | |
CRTAP | ENST00000449224.1 | c.92A>G | p.Tyr31Cys | missense_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151874Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000472 AC: 1AN: 211940Hom.: 0 AF XY: 0.00000843 AC XY: 1AN XY: 118574
GnomAD4 exome AF: 0.0000125 AC: 18AN: 1438484Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 10AN XY: 715924
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151874Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74190
ClinVar
Submissions by phenotype
Osteogenesis imperfecta type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 05, 2017 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CRTAP-related disease. This variant is present in population databases (rs372115693, ExAC 0.002%). This sequence change replaces tyrosine with cysteine at codon 31 of the CRTAP protein (p.Tyr31Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at